ABSTRACT
OBJECTIVE To establish the method for content determination of related substances in Oxcarbazepine tablets. METHODS Ultra-high performance liquid chromatography （UPLC） method was adopted and the separation was performed on ZORBAX Eclipse Plus C18 column with mobile phase consisted of acetonitrile-0.01 mol/L ammonium acetate solution （pH6.0） （gradient elution） at the flow rate of 0.5 mL/min. The detection wavelength was 230 nm and column temperature was set at 35 ℃. The sample size was 10 μL. RESULTS The linear ranges of oxcarbazepine and impurity A， B， C， D， E， I， K， L and N were 0.192-1.440， 1.019-7.639， 0.208-1.559， 0.230-1.727， 0.389-2.915， 0.182-1.364， 0.393-2.945， 0.199-1.493， 0.199-1.490 and 0.200- 1.503 μg/mL， respectively （all r＞0.999）. The detection limits were 0.046， 0.037， 0.049， 0.027， 0.077， 0.040， 0.114， 0.054， 0.055 and 0.039 μg/mL. The quantitation limits were 0.152， 0.122， 0.162， 0.090， 0.258， 0.132， 0.380， 0.181， 0.185 and 0.130 μg/mL. RSDs of precision， repeatability， stability （24 h） and durability tests were all lower than 5.0%. The average recoveries were 92.8%-105.6% （RSD≤3.0%， n＝9）. Only impurity K and unknown impurity were detected in the original preparation sample， with a total content of 0.078% to 0.083%； impurities A， B， D， I and unknown impurity were detected in the generic preparations produced by domestic enterprise Ⅰ， with a total content of 0.147% to 0.163%； impurities A， B， I and unknown impurity were detected in the generic preparations produced by domestic enterprise Ⅱ， with a total content of 0.085% to 0.161%. CONCLUSIONS The established method is rapid， sensitive， accurate， stable and durable. It can be used for the content determination of 9 known impurities in Oxcarbazepine tablets.
ABSTRACT
Dos formulaciones de oxcarbazepina (Trileptal®, Novartis, y Oxcarbazepina®, Tecnoquímicas S. A.), previamente demostradas como equivalentes farmacéuticos, fueron evaluadas en cuanto a bioequivalencia por medio de un estudio aleatorizado, cruzado, en dos períodos, con dosis oral única de 1.200 mg, en 24 hombres adultos voluntarios sanos entre 18-35 años. Se evaluaron los siguientes parámetros farmacocinéticos: Área bajo la curva (AUC), Concentración máxima (Cmáx) y Tiempo para alcanzar la concentración máxima (Tmáx). Hubo un intervalo de lavado de siete días entre los dos períodos. Las concentraciones plasmáticas se evaluaron por HPLC/UV con el método de la adición estándar. No se encontraron diferencias significativas entre las dos preparaciones. Se concluyó que las dos preparaciones son equivalentes farmacéuticos y bioequivalentes y que, en consecuencia, son intercambiables para propósitos terapéuticos.
Two formulations of oxcarbazepine (Trileptal®, Novartis, y Oxcarbazepina®, Tecnoquímicas S. A.), previously shown to be pharmaceutical equivalents, were evaluated concerning their bioequivalence by means of a randomized, crossover, single oral dose (1.200 mg), two-period study in 24 healthy adult males. The following pharmacokinetic parameters were determined: Area under the curve (AUC), Maximal concentration (Cmax), and Time to reach maximal concentration (Tmax). There was a wash-out interval of seven days between the two periods. Plasmatic concentrations of the drug were measured with HPLC/UV with standard addition. No significant differences were found between the two preparations. It was concluded that they are pharmaceutical equivalents as well as bioequivalent. Consequently, they are interchangeable for therapeutic purposes.